An acute shortage of donor organs greatly limits access to transplantation. As of Jul. 22, 1992, according to the United Network for Organ Sharing (UNOS), 21,120 patients were awaiting a kidney; 2,183 a liver; 783 a pancreas; 2,557 a heart; 166 a heart-lung; and 889 a lung transplant. Since December 1986, the demand for transplantation has increased by 188%, from 9,632 to 27,678 potential recipients. Meanwhile, there has been little change in the supply of organ donors. Between 1986 and 1991, the number of donors has been between 4,000 and 4,500 annually. As a result, the number of patients who die while awaiting a transplant continues to increase: from 1,537 in 1988 to 2,077 in 1990, with variation according to the procedure required.
The paucity of donor organs for human transplantation can be remedied to a certain extent by procuring organs from distant sites, particularly from large urban areas where accident rates are high. Heart and lung transplantations would benefit greatly, as has been the case for renal transplantation, from the development of satisfactory methods of organ preservation to extend the travel time of donor organs.
The criteria for lung donors are very strict; only 10% to 15% of suitable heart donors will also be potential lung donors. With current clinical methods of lung preservation, 4 to 6 hours of storage proves largely successful, and sometimes a period of ischemia of up to 9 hours is tolerated with depressed lung function after transplant. Several investigators have reported preservation for periods ranging from 20 to 48 hours, but none of these reports has been associated with consistent, reliable results, which would be required for clinical application. Methods with such a short preservation time have three primary disadvantages: (1) they limit the geographic area from which grafts can be obtained; (2) they limit the time available for histocompatibility tests; and (3) they increase the likelihood of inadequate organ function after transplantation.
Clinical methods used for lung preservation for transplantation have included immediate implantation (donor transported to the hospital where the recipient is located); hypothermic atelectasis, hypothermic pulmonary artery flushing and storage, with or without varying degrees of inflation; donor core cooling on cardiopulmonary bypass; and autoperfused heart-lung preparation at normothermia.
Single-flush perfusion of the lungs is currently the most widely practiced technique in lung preservation. However, when simple flushing with preservation solution is used, the result is always unsatisfactory. Even with many different additives and modifications to the solution, lung function is severely compromised after more than 12 hours of preservation. For years, numerous chemicals (such as prostaglandins, oxygen free-radical scavengers, platelet activating factor antagonists or leukocyte depletion, corticosteroids, and other chemicals) have been added to pulmonary artery flush solutions such as modified Euro-Collins solution, University of Wisconsin solution, UCLA solution, Stanford solution, and Bretschneider's solution. Although various reports have indicated that these added chemicals provide improved effects, no additive has been proved reliable. Our results from Group 2 (described elsewhere) appear to agree with previous studies. Euro-Collins solution alone is known to cause pulmonary vasoconstriction, and the safe preservation time is usually 4 to 6 hours.
Long-termpreservation of donor organs in vitro will also make it possible to treat the donor organ before it is transplanted, thus reducing or possibly eliminating the necessity for immunosuppressive treatment of the recipient.
Our previous study showed that DADLE can effectively extend tissue survival time in a normothermic multiorgan preservation block. Because of technical difficulties, normothermic multiple organ preparations are used by only a few groups around the world; the use of DADLE in such preparations is limited at the present time. However, if DADLE can also extend tissue survival time in hypothermic storage, the potential of adding positive effects to presently used preservation solutions will be tremendous. Not only will this technique improve hypothermic organ preservation, but it will also improve the effectiveness of various currently used cardioplegic solutions and possibly of other hypothermic treatment modalities.